The overall goal of this research is to develop technology for imaging uterine masses and identifying diffuse pathological conditions using ultrasound strain imaging or elastography. Postmenopausal bleeding is a common gynecological problem, accounting for nearly 5% of office visits. Though the majority of cases result from a benign etiology (endometrial atrophy or hyperplasia, polyps, leiomyomas), approximately 10% to 30% of women will be found to have endometrial cancer. One of the features of cancer is the relative rigidity of the surrounding neoplastic tissue. We hypothesize that elastography could usefully be applied to the diagnosis of postmenopausal bleeding by distinguishing diffuse stiff endometrial tissue (cancer), diffuse endometrial soft tissue (hyperplasia), focal stiff masses (leiomyomas), and focal soft masses (polyps). Differentiation between fibroids and adenomyosis in the uterus is another area where stiffness variation may provide a means of diagnosis. Uterine fibroids and adenomyosis have a similar appearance on conventional US scans, making differentiation problematic- if not impossible- for the sonologist. This differentiation is, however, clinically important because treatment for the two conditions is very different, and clinicians must now use more expensive but less accessible imaging tests. Our research will develop ultrasound strain imaging for differentiating between these two conditions. Three specific aims are proposed in the R21 phase of this research. The first investigates the stiffness contrast that is present between normal and abnormal uterine tissue. Young's modulus measurements will be done on excised uterine samples obtained following hysterectomy procedures. Secondly, strategies for optimizing the timing between mechanical deformation and data acquisition in the uterus for in vivo saline induced sonohysterography (SIS) based strain imaging will be studied using anthropomorphic phantoms. Phantoms will also be utilized to optimize displacement tracking and strain estimation performance with the multi-level algorithm proposed for sector strain imaging. Thirdly, the research will also investigate the feasibility of utilizing SIS based strain imaging in-vivo. This will be done by applying the method to 15-20 human patients and evaluating uterine mass delineation/ differentiation and the ability to identify diffuse uterine pathology. Exvivo strain images will be obtained of intact uterine specimens when they become available for comparisons with these in-vivo imaging results. Preliminary in-vivo results presented in the proposal (Fig. 10 and 11) strongly indicate that our approaches will be effective. Thus, this feasibility project will likely lead to future in depth clinical trials. PUBLIC HEALTH RELEVANCE STATEMENT: Postmenopausal bleeding is a common gynecological problem, accounting for nearly 5% of office visits. Though the majority of cases result from benign etiology approximately 10% to 30% of women will be found to have endometrial cancer. One of the features of cancer is the relative rigidity of the surrounding tissue. We hypothesize that elastography could usefully be applied to the diagnosis of postmenopausal bleeding by distinguishing diffuse stiff endometrial tissue (cancer), diffuse endometrial soft tissue (hyperplasia), focal stiff masses (fibroids), and focal soft masses (polyps).